The immune response as a double‐edged sword: The lesson learnt during the <scp>COVID</scp>‐19 pandemic

Agrati, Chiara; Carsetti, Rita; Bordoni, Veronica; Sacchi, Alessandra; Quintarelli, Concetta; Locatelli, Franco; Ippolito, Giuseppe; Capobianchi, Maria Rosaria

doi:10.1111/imm.13564

Cited by 19 publications

(7 citation statements)

References 167 publications

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“…At the same time, recent studies have demonstrated that the development of an effective immune response should be balanced, implying the simultaneous concordant release of both pro- and anti-inflammatory cytokines [ 5 ]. An unbalanced release of proinflammatory cytokines may lead to a “cytokine storm” [ 2 ] similar to the cytokine storm in COVID-19 infection [ 6 ]. A systemic inflammatory reaction (acute or chronic) limits the resolution of inflammation and causes disease progression and tissue damage, affecting all organs and systems of the host body [ 3 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Nosik

Belikova

Ryzhov

et al. 2023

Viruses

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HIV-1 infection is characterized by aberrant immune activation, and infection with M. tuberculosis by an unbalanced production of proinflammatory cytokines. The expression of these cytokines in HIV-1/TB coinfection is still understudied. Here, we aimed to compare the production of proinflammatory cytokines in drug-naive patients coinfected with HIV-1 and M. tuberculosis (HIV/TB) compared to patients with respective monoinfections. Plasma samples of patients with HIV/TB coinfection (n = 36), HIV-1 monoinfection (n = 36), and TB monoinfection (n = 35) and healthy donors (n = 36) were examined for the levels of eight proinflammatory cytokines. Their levels were significantly increased in all patient groups compared to healthy donors. At the same time, a drastic decrease in the plasma levels of IFN-γ, TNF-α, Il-1β, IL-15, and IL-17 was detected in patients with HIV/TB coinfection compared to patients with HIV-1 or TB monoinfections. The plasma levels of IL-17 characterized the TB severity: in HIV/TB-coinfected patients with disseminated TB, plasma levels of IL-17 were eight times lower than in patients with less severe TB forms (infiltrative TB or TB of intrathoracic lymph nodes; p < 0.0001). At the same time, HIV/TB-coinfected patients had increased plasma levels of IL-8, IL-12, and IL-18, with the levels of IL-8 correlating with mortality (p < 0.0001). Thus, on the contrary to the patients with HIV-1 or TB monoinfections, HIV/TB-coinfected patients had suppressed production of most of the proinflammatory cytokines associated with antimicrobial immune response, specifically of T-cells involved in the containment of both infections. At the same time, they demonstrated an expansion of proinflammatory cytokines known to originate from both hematopoietic and nonhematopoietic cells, and manifest tissue inflammation. In HIV-1/TB coinfection, this leads to the disruption of granuloma formation, contributing to bacterial dissemination and enhancing morbidity and mortality.

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Section: Introductionmentioning

confidence: 99%

Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Nosik

Belikova

Ryzhov

et al. 2023

Viruses

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“…Endothelial cells, von Willebrand/ADAMTS13 axis, coagulation factors, fibrinolytic system, immunothrombosis, inflammatory cytokines, and anti-phospholipid antibodies are all involved in its determination [ 5 ]. We can just hypothesize a possible protective role of vaccination through an action on the immune system, modulating the inflammation-coagulation interface [ 6 ]. The hypothesis of a possible protective role of vaccination in preventing PE in hospitalized COVID-19 patients has not been explored.…”

Section: Discussionmentioning

confidence: 99%

Does COVID-19 vaccination protect against pulmonary embolism?

Tantillo

Cilloni

Guarnera

et al. 2023

J Anesth Analg Crit Care

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The prevalence of venous thromboembolism (VTE) in COVID-19 patients is highly variable, depending on methodological and clinical factors, among which vaccination (1). The hypothesis of a possible protective role of vaccination in preventing pulmonary embolism (PE) in hospitalized COVID-19 patients has not been explored. The aim of the study was to evaluate PE prevalence in vaccinated versus unvaccinated hospitalized COVID-19 patients. We conducted a retrospective case–control study from 2021/11/01 to 2022/01/15; we reviewed all the chest computed topographies (chest-CT) performed because of a clinical suspicion for PE at our Institution. Sixty-two patients were included in the study: 27/62 (43.5%) were vaccinated and 35/62 (56.4%) were not. Vaccinated patients were older and with more comorbidities than unvaccinated people. Overall, PE was diagnosed in 19/62 patients (30.1% prevalence). CT Severity Score (CT-SS) differs between the two groups; not vaccinated patients had a more severe CT imaging than the vaccinated (< 0.00005). PE prevalence in ICU was 43.2% (16/37 patients), while in the Internal Medicine ward, it was 12% (3/25 cases). PE was significantly higher among unvaccinated people: 16/35 (45.7%) vs 3/27 (11.1%), OR p = 0.04. We observed a strong association between vaccination and protection from PE in hospitalized COVID-19 patients: morbidity was significantly lower in vaccinated versus not vaccinated patients. The issue of the protective role of vaccination in COVID-19-associated VTE should be addressed in adequately designed and powered future prospective studies.

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“…Flaviviruses, Filoviruses, SARS-CoV-2, etc.) is the role of early uncontrolled cytokine storm as the main driver of tissue damage, leading to immune-mediated multi-organ injury and disease progression (7)(8)(9)(10). In this scenario, we could speculate that immunosuppression could paradoxically have a beneficial effect, dampening the excessive inflammatory response and reducing the immune-mediated damage (11).…”

Section: The Immune Response In Ic Patients: a Complex Scenariomentioning

confidence: 99%

Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response

et al. 2023

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The immune response to invading pathogens is characterized by the rapid establishment of a complex network of cellular interactions and soluble signals. The correct balancing of activating and regulating pathways and tissue-homing signals determines its effectiveness and persistence over time. Emerging viral pathogens have always represented a great challenge to the immune system and an often uncontrolled/imbalanced immune response has been described (e.g. cytokine storm, immune paralysis), contributing to the severity of the disease. Several immune biomarkers and cell subsets have been identified as major players in the cascade of events leading to severe diseases, highlighting the rationale for host-directed intervention strategy. There are millions of immunocompromised pediatric and adult patients worldwide (e.g. transplant recipients, hematologic patients, subjects with primary immune-deficiencies), experiencing an impaired immune reactivity, due to diseases and/or to the medical treatments. The reduced immune reactivity could have two paradoxical non-exclusive effects: a weak protective immunity on one hand, and a reduced contribution to immune-mediated pathogenetic processes on the other hand. In these sensitive contexts, the impact of emerging infections represents a still open issue to be explored with several challenges for immunologists, virologists, physicians and epidemiologists. In this review, we will address emerging infections in immunocompromised hosts, to summarize the available data concerning the immune response profile, its influence on the clinical presentation, the possible contribution of persistent viral shedding in generating new viral variants with improved immune escape features, and the key role of vaccination.

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The immune response as a double‐edged sword: The lesson learnt during the COVID‐19 pandemic

Cited by 19 publications

References 167 publications

Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection

Does COVID-19 vaccination protect against pulmonary embolism?

Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response

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